Kathryn Skelly, MD, MSc
Internal Medicine Resident , Maine Medical Center
American College of Physicians Maine Chapter
2013 Annual Chapter Educational Meeting
September 28, 2013
D.P. : 44 year old male
 HPI:
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Polyarthralgias for 1 day (shoulders, hands, knees)
Fever to 100.9 and “flu-like symptoms”
Acute on chronic bilateral knee effusions
No known tick exposure or rash
Not sexually active. No penile discharge or dysuria
No known family history of rheumatologic disease
Uses medical marijuana but denied other drug use
 ROS:
 Mild headache earlier in the week that had resolved
 Denied cough, sore throat, shortness of breath, chest
pain, abdominal pain, nausea, vomiting, diarrhea.
History
 Past Medical History:
 Osteoarthritis (spine and knees)
 GERD
 Medications:
 Morphine 30 mg QID (chronic back and knee pain)
 Pantoprazole 40 mg BID
 Medical marijuana
 Allergies: Celebrex, nexium
 Social History:
Works as a landscaper.
Single
4 drinks of alcohol daily. No tobacco
Marijuana as above
No recent travel outside Maine.
 Family History:
 Patient unsure of family history
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Physical Exam
 VS: 37.3; 137/89; 91; 18; 94% on room air
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General: Well-appearing
HEENT: No lymphadenopathy
Regular heart rhythm. No murmurs, rubs, or gallops
Lungs clear to auscultation bilaterally
Benign abdominal exam
Musculoskeletal and Neurologic exams:
 Visible trapezius and rhomboid muscle spasms.
 No bony point tenderness to palpation along the spine.
 Pain with bilateral upper extremity abduction, but full range
of motion
 Strength 5/5 in upper and lower extremities
 No warmth or erythema of knees, but effusions present
Laboratory Assessment
4.8
12.7
157
139 103
9
4.0
0.70
29
36.5
 ESR: 48
 Total CK: 78
 Alk phos: 97
 AST: 35
 ALT: 47
101
Plan:
 Patient diagnosed with likely viral
reactive arthritis
 Treated with prednisone 40 mg daily
for 6 days, and oxycodone for pain.
Second Presentation
 HPI:
 Presents to ED with worsening bilateral
shoulder pain, low back pain, and knee pain
 He took prednisone as prescribed
 Has been taking extra morphine, and reports
that pain is still “16/10”
 Denied fevers
 Denied IV drug use or tick exposure.
Physical Exam
 VS: T 36.8, P 89, BP 156/89, RR 18, 98% on RA
 Notable for hyperesthesia of skin over
shoulders and trapezius muscles
 Swelling and erythema over AC joints
bilaterally, with “exquisite” tenderness to
palpation.
 Bilateral knee effusions noted. No rash.
 Patient referred to rheumatology
Third Presentation
 HPI
 Patient presents with worsening joint
pain
 Back pain and knee pain now so severe,
patient can’t get out of bed or ambulate
 Family called 911 because patient was
having rigors at home.
Physical Exam
 VS: 38.3, BP: 141/76, P: 88, RR: 22, 96% on
RA
 Warmth and effusions of both knees and right
elbow
 tenderness and warmth over both AC joints with
decreased range of motion of shoulders
 Tenderness along L5-S1 interspace
 Limited neurologic exam secondary to patient’s
extreme pain
 No rash noted
Laboratory Results
8.2
11.3
231
32.6
 ESR:
73
 CRP: 22.71
 CMP within normal limits
 Blood cultures sent
 Right knee aspirated
Differential Diagnosis?
Our Differential Diagnosis
Infection:
Endocarditis
Bacteremia and septic arthritis
Osteomyelitis of the spine
Disseminated gonococcal infection
Tick-borne illness
Viral Infection (parvovirus, hepatitis)
Inflammatory
Arthritis:
Rheumatoid arthritis
SLE
Polymyalgia rheumatica
Spondyloarthropathy
Crystal arthropathy
Reactive arthritis
Data
 MRI cervical spine:
 Epidural and pre-vertebral abscess at C6-7
 MRI lumbar spine:
 Septic facet arthropathy at L4-5 with 9X17 mm
abscess extending into the right subarticular
recess and posterior paraspinal muscle
 Patient started on vancomycin, ceftriaxone,
metronidazole
 Neurosurgery and infectious disease consults
MRI Lumbar Spine
MRI Cervical Spine
More Data:
 Right knee aspirate:
 13,200 leukocytes
88% PMN
 12% lymphocytes
 No crystals seen
 Gram stain negative, culture no growth
Hepatitis panel negative
CCP Ab <6 (negative)
RF 19 (0-13)
ANA <1:80
Parvovirus: IgG Ab positive, IgM Ab negative
Lyme disease Ab: IgG, IgM negative
HIV negative
ANCA negative
Chlamydia, gonorrhea negative
TEE: Structurally normal valves, with no evidence of vegetations
Blood cultures negative at 48 hours, 2 sets
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Hospital Course
 CRP up to 29.35 (from 22.7 )
 Hospital day #3:
 Blood cultures from admission now positive for
gram negative rods (2/2)
 Patient changed to cefepime (still on
vancomycin and metronidazole)
 Patient reveals more history:
 Pets: iguanas and snakes at home
 What are you thinking now?
Hospital Course
 Blood cultures:
 Gram negative rods
 Suspected anaerobic activity
 Possible organisms:
Salmonella
 Bacteroides
 Prevotella
 Fusobacterium
 Hospital Day #5
 Patient reports that several days before symptoms
started, he was bitten by a live rat while feeding it to his
pet snake (hospital admission was about 11 days after the
bite)
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Working Diagnosis
 “Rat bite fever”
 Organism on gram stain resembles Streptobacillus
moniliformis
 Still awaiting final speciation
 Still on cefepime and metronidazole
 Likely septic polyarthritis (knees and AC joints) despite
negative culture of aspirate
 Fastidious organism
 WBC in aspirate likely low due to initial course of prednisone
 Epidural abscesses
 Followed by neurosurgery No surgical intervention
Final Diagnosis:
 “Rat bite fever”, with cervical and lumbar epidural
abscesses, osteomyelitis, and septic polyarthritis
 Hospital Day #16, final speciation on blood cultures:
 Streptobacillus moniliformis Identified in collaboration between
MMC and Mayo Clinic
 Patient changed to IV penicillin G Q4 hours
 HD #21: Patient discharged to rehab on IV penicillin
therapy with weekly ID follow up
Rat Bite Fever
Rat Bite Fever
 Three Clinical Syndromes:
 Streptobacillus moniliformis infection
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Accounts for most cases in the United States
 Spirillum minus (sodoku)
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Mostly in Asia, but found worldwide
 Haverhill Fever
 First reported in the U.S. in 1914
 Causal organism named Streptobacillus moniliformis
in 1925
Streptobacillus Moniliformis
 Pleomorphic
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filamentous bacilli
Characteristic bulbous
swelling in chains and
tangled clumps
Fastidious
Slow growing
 Must hold cultures at
least 5 days
Aerobic and facultatively
anaerobic
Torres et al. 2001
Haverhill Fever
 Streptobacillus moniliformis infection via
ingestion of contaminated food
 Contamination with infected excreta
or saliva
 Typical features:
 Absence of known rat exposure
 Large number of patients
 Common geographical and temporal
exposure
 First described in 1926…
Outbreak in Haverhill, MA: 1926
 86 patients developed symptoms over a 4 week period
 Symptoms:
 Abrupt, severe fever and chills
 Nausea, vomiting, headache
 Arthritis (>6 joints in 50% of patients)
 Relapsing and remitting rash
Macular or papular, petechial; wrists, arms, feet, ankles
 Identified source of infection: raw milk
 92% of patients had received raw milk from local bottling plant
 Suspected possible contamination from rat urine
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Rat Bite Fever: Epidemiology
 2 million animal bites per year in the U.S.
 1% are rat bites
 Incidence likely very underestimated
 Rat bite fever is not a reportable disease
 Generally low clinical suspicion
 Difficult to culture
 Typical patient profile:
 Historically, children living in poverty
 Demographics changing
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Children (pet rat), pet store workers, animal lab personnel
Disease Transmission
 Found predominantly in nasal and oropharyngeal flora of rats
 10-100% of domesticated and lab rats
 50-100% wild rats
 Infection and colonization documented in other species:
 Guinea pigs, gerbils, ferrets, cats, dogs, mice
 Infection resulting from:
 Rat bite
 Rat scratch
 Handling infected rat (can be transmitted via infected saliva)
 Ingesting food/water contaminated with infected rat feces
 Exposure in cases of infection can be unknown
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Possible infection from dog bite after dog had contact with rat:
 (Wouters et al 2008): 3/18 dogs who had proven contact with rats were
found to have Streptobacillus moniliformis in their mouth
Graves and Janda (2001)
 Microbial Diseases Laboratory,
State of California:
 Documented cases of human
infection with Streptobacillus
moniliformis from 1970-1998
 N=45
 Rat exposure:
 Bite, scratch, kiss, other rat
association
Animal Exposure
Percentage
of Patients
Pet rat
54
School rat
14
Other rat exposure
11
Wild rat
9
Mouse
3
Squirrel
3
Exposure not known
6
Clinical Manifestations
 Symptoms start 3-7 days following exposure (can be up to 21 days)
 Fever (intermittent)
Presenting Symptoms
Percentage of
 Myalgias, arthralgias
Patients
 Vomiting
 Headache
Fever
88
 Polyarthritis (can last years) Arthritis/Arthralgia
73
 Sore throat
Rash
65
 Serious complications
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Meningitis
Endocarditis
Myocarditis
Pneumonia
Septic arthritis
Bacteremia
Multiple organ failure
Fatigue/Malaise
20
Headache
18
Chills
15
(Graves and Janda, 2001)
Epidural Abscess and Streptobacillus moniliformis: One
Case Report in the Literature (Addidle et al., 2012)
 58 year old male presented with 2 weeks back pain, fevers,
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lower extremity weakness
MRI: Large epidural abscess (L4-S1)
Urgently went to OR
Culture from abscess negative, but blood cultures grew
gram negative rods:
 Patient treated empirically for Capnocytophaga spp. due
to history of his dog licking a wound
After 21 days, organism identified as Streptobacillus
moniliformis.
Patient treated with 5 weeks IV ceftriaxone
Diagnosis
 Consider in any patient with unexplained febrile
illness, with rash and/or polyarthritis
 Particularly if rat or other rodent exposure
 Blood or synovial fluid
 Alert lab, so they can optimize media and
culture
 Incubate cultures for 21 days
 Serologic testing not available
Treatment
 Mortality rate 13% without treatment
 Treatment of choice:
 IV penicillin 400,000-600,000 IU (240-360 mg)
per day
 Add streptomycin or gentamicin for
endocarditis
 Alternatives: Tetracycline, doxycycline,
streptomycin
 Cephalosporins have been used successfully
 Duration of therapy is individualized
D.P. Clinical Course
 After 6 weeks:
 Still on IV Penicillin
 Continues to have severe back and knee
pain
 CRP: 4.95
 Follow up MRI after 3 months:
 Epidural abscesses had resolved
 Multilevel osteomyelitis, discitis and
inflammatory changes improving
D.P. Clinical Course
 After 5 months:
 On oral Penicillin (500 mg QID)
 MRI shows stable disease in cervical
spine, but progression of osteomyelitis in
the lumbar spine
 CRP 0.21
 IR guided biopsy of L5 facet pending…
5 Month MRI Lumbar Spine
Considerations for the Future:
Zoonoses on the Rise?
 Changing planet:
 Human wildlife conflict
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Habitat loss, dissolving boundaries
Commercial bushmeat hunting worldwide
 Urbanization of previously rural areas
 Global poverty
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Lack of clean water supply, sanitary food
 Black market wildlife trade
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Exotic pets
Animal parts
Consumption
References
 Addidle et al. 2012. Epidural Abscess Caused by Streptobacillus
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moniliformis. Journal of Clinical Microbiology; 50(9): 3122-3124.
Elliot, S. 2007. Rat Bite Fever and Streptobacillus moniliformis. Clinical
Microbiology Reviews. P. 13-22.
Graves and Janda, 2001. Rat-Bite Fever (Streptobacillus moniliformis): A
Potential Emerging Disease. Int J Infect Dis; 5:151-154.
Wouters et al, 2008. Dogs as Vectors of Streptobacillus moniliformis
infection? Vet Microbiol; 128(3-4): 419-22.
Torres et al, 2001. Remitting Seronegative Symmetrical Synovitis with
Pitting Edema Associated with Subcutaneous Streptobacillus
moniliformis Abscess. Journal of Rheumatology 2001; 28: 1696-8.